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https://hdl.handle.net/2440/129230
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Type: | Journal article |
Title: | Inflammation-induced IgA⁺ cells dismantle anti-liver cancer immunity |
Other Titles: | Inflammation-induced IgA(+) cells dismantle anti-liver cancer immunity |
Author: | Shalapour, S. Lin, X.-J. Bastian, I.N. Brain, J. Burt, A.D. Aksenov, A.A. Vrbanac, A.F. Li, W. Perkins, A. Matsutani, T. Zhong, Z. Dhar, D. Navas-Molina, J.A. Xu, J. Loomba, R. Downes, M. Yu, R.T. Evans, R.M. Dorrestein, P.C. Knight, R. et al. |
Citation: | Nature, 2017; 551(7680):340-345 |
Publisher: | Springer Nature |
Issue Date: | 2017 |
ISSN: | 0028-0836 1476-4687 |
Statement of Responsibility: | Shabnam Shalapour, Xue-Jia Lin, Ingmar N. Bastian, John Brain, Alastair D. Burt, Alexander A. Aksenov, Alison F. Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani, Zhenyu Zhong, Debanjan Dhar, Jose A. Navas-Molina, Jun Xu, Rohit Loomba, Michael Downes, Ruth T. Yu, Ronald M. Evans, Pieter C. Dorrestein, Rob Knight, Christopher Benner, Quentin M. Anstee, Michael Karin |
Abstract: | The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8+ T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8+ T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA+ cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8+ T-lymphocyte activation as a tumour-promoting mechanism. |
Keywords: | Plasma cells |
Rights: | © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
DOI: | 10.1038/nature24302 |
Published version: | http://dx.doi.org/10.1038/nature24302 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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